Pei-Fang Su

IMPORTANCE: Targeting oncogenic drivers (genomic alterations critical to cancer development and maintenance) has transformed the care of patients with lung adenocarcinomas. The Lung Cancer Mutation Consortium was formed to perform multiplexed assays testing adenocarcinomas of the lung for drivers in 10 genes to enable clinicians to select targeted treatments and enroll patients into clinical trials. OBJECTIVES: To determine the frequency of oncogenic drivers in patients with lung adenocarcinomas and to use the data to select treatments targeting the identified driver(s) and measure survival. DESIGN, SETTING, AND PARTICIPANTS: From 2009 through 2012, 14 sites in the United States enrolled patients with metastatic lung adenocarcinomas and a performance status of 0 through 2 and tested their tumors for 10 drivers. Information was collected on patients, therapies, and survival. INTERVENTIONS: Tumors were tested for 10 oncogenic drivers, and results were used to select matched targeted therapies. MAIN OUTCOMES AND MEASURES: Determination of the frequency of oncogenic drivers, the proportion of patients treated with genotype-directed therapy, and survival. RESULTS: From 2009 through 2012, tumors from 1007 patients were tested for at least 1 gene and 733 for 10 genes (patients with full genotyping). An oncogenic driver was found in 466 of 733 patients (64%). Among these 733 tumors, 182 tumors (25%) had the KRAS driver; sensitizing EGFR, 122 (17%); ALK rearrangements, 57 (8%); other EGFR, 29 (4%); 2 or more genes, 24 (3%); ERBB2 (formerly HER2), 19 (3%); BRAF, 16 (2%); PIK3CA, 6 (<1%); MET amplification, 5 (<1%); NRAS, 5 (<1%); MEK1, 1 (<1%); AKT1, 0. Results were used to select a targeted therapy or trial in 275 of 1007 patients (28%). The median survival was 3.5 years (interquartile range [IQR], 1.96-7.70) for the 260 patients with an oncogenic driver and genotype-directed therapy compared with 2.4 years (IQR, 0.88-6.20) for the 318 patients with any oncogenic driver(s) who did not receive genotype-directed therapy (propensity score-adjusted hazard ratio, 0.69 [95% CI, 0.53-0.9], P = .006). CONCLUSIONS AND RELEVANCE: Actionable drivers were detected in 64% of lung adenocarcinomas. Multiplexed testing aided physicians in selecting therapies. Although individuals with drivers receiving a matched targeted agent lived longer, randomized trials are required to determine if targeting therapy based on oncogenic drivers improves survival. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01014286.

OBJECTIVE: Developing country-specific unit-cost catalogs is a key area for advancing economic research to improve medical and policy decisions. However, little is known about how health care costs vary by type 2 diabetes (T2D) complications across time in Asian countries. We sought to quantify the economic burden of various T2D complications in Taiwan. RESEARCH DESIGN AND METHODS: A nationwide, population-based, longitudinal study was conducted to analyze 802,429 adults with newly diagnosed T2D identified during 1999-2010 and followed up until death or 31 December 2013. Annual health care costs associated with T2D complications were estimated, with multivariable generalized estimating equation models adjusted for individual characteristics. RESULTS: The mean annual health care cost was $281 and $298 (2017 U.S. dollars) for a male and female, respectively, diagnosed with T2D at age <50 years, with diabetes duration of <5 years, and without comorbidities, antidiabetic treatments, and complications. Depression was the costliest comorbidity, increasing costs by 64-82%. Antidiabetic treatments increased costs by 72-126%. For nonfatal complications, costs increased from 36% (retinopathy) to 202% (stroke) in the event year and from 13% (retinopathy or neuropathy) to 49% (heart failure) in subsequent years. Costs for the five leading costly nonfatal subtype complications increased by 201-599% (end-stage renal disease with dialysis), 37-376% (hemorrhagic/ischemic stroke), and 13-279% (upper-/lower-extremity amputation). For fatal complications, costs increased by 1,784-2,001% and 1,285-1,584% for cardiovascular and other-cause deaths, respectively. CONCLUSIONS: The cost estimates from this study are crucial for parameterizing diabetes economic simulation models to quantify the economic impact of clinical outcomes and determine cost-effective interventions.

PURPOSE: Although Recepteur d'Origine Nantais (RON), a member of the MET receptor tyrosine kinase family, is overexpressed and constitutively active in some primary tumors and tumor cell lines, its expression pattern and clinical significance in colorectal cancer are not well documented. METHODS: By using immunohistochemical staining, we examined RON and MET expression in 135 colorectal cancer specimens and investigated the association of the immunoreactivity of both receptors with colorectal cancer clinical parameters and prognosis. RESULTS: We found moderate to strong expression in 99 cases (73 percent) for RON and 97 cases (72 percent) for MET. Univariate analysis showed that increased immunoreactivity of RON or MET was associated with shorter patient survival and that moderate to strong coexpression of both receptors was associated with a significantly worse prognosis. Multivariate Cox analysis showed that the risk of tumor recurrence for patients with high-RON/high-MET expression was approximately 11 times greater than for patients with low-RON/low-MET expression (P = 0.001). In addition, RON and MET expression levels were positively correlated (P <or= 0.001; tau = 0.306). CONCLUSIONS: The crosstalk between RON and MET in colorectal cancer seems important. Evaluating the expression patterns of RON and MET was predictive of clinical outcome for patients with colorectal cancer.